Context: Patients with newly diagnosed high-risk DLBCL have suboptimal outcomes. Subcutaneous epcoritamab is a CD3xCD20 bispecific antibody well suited for combination with standard of care therapies. Objective: Evaluate safety and efficacy of epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated patients with high-risk DLBCL in arm 1 of a phase 1/2, open-label trial (EPCORE NHL-2; NCT04663347). Patients: Adults with previously untreated CD20+ DLBCL and IPI ≥3 were included. As of December 1, 2021, 33 patients (median age, 66 y) had enrolled. Interventions: Patients received subcutaneous epcoritamab (QW, cycles 1–4; Q3W, cycles 5–6) + R-CHOP for 6 cycles (21 d) followed by epcoritamab monotherapy Q4W up to 1 y (in cycles of 28 d). Step-up dosing and corticosteroid prophylaxis were required. Results: All 33 patients treated (epcoritamab 24 mg, n=4; 48 mg, n=29) had IPI ≥3, and ≥24% had double/triple-hit DLBCL. Median follow-up was 3 mo (range, 0–9.7), median number of total cycles initiated was 5 (1–13), and 94% of patients (31/33) remained on treatment. Treatment-emergent AEs (TEAEs) in ≥35% of patients were neutropenia (48%; febrile neutropenia in 9% of all patients), CRS (45%), infections (42%), anemia (39%), and injection-site reactions (36%). No TEAEs led to epcoritamab discontinuation. Most CRS events were low grade (42% grade [G] 1–2, 3% G3), occurred in cycle 1, and resolved after a median of 2 d (1–11); 4 patients received tocilizumab. G2 ICANS occurred in 1 patient. No fatal TEAEs occurred. In efficacy-evaluable patients, the overall response rate (ORR) was 96% (24/25); 68% (17/25) had complete metabolic response (CMR) by PET-CT. In the 10 patients who completed 6 cycles of R-CHOP by the cutoff date, ORR and CMR rate were 100% and 90%, respectively; all patients remained in response at data cutoff (longest duration of response, 7.1+ mo, ongoing). Conclusions: Epcoritamab + R-CHOP had manageable safety, mostly low-grade CRS that did not lead to treatment discontinuation, and high response rates in patients with previously untreated DLBCL. Updated data will be presented. Funding: This study was funded by Genmab A/S and AbbVie.
- Phase I/II
- diffuse large B-cell lymphoma
- hematologic malignancy
- non-Hodgkin lymphoma